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cyromazine Registration of the Major Change in Labeling for Cyromazine, Contained in the Pesticide Product Trigard Insecticide 4/05

New York State Department of Environmental Conservation
Division of Solid & Hazardous Materials

Bureau of Pesticides Management
Pesticide Product Registration Section
625 Broadway, Albany, New York 12233-7257
Phone 518-402-8768     FAX 518-402-9024
Website: http://www.dec.state.ny.us/website/dshm/pesticid/pesticid.htm
E-Mail: ppr@gw.dec.state.ny.us

April 7, 2005

CERTIFIED MAIL
RETURN RECEIPT REQUESTED


John D. Abbott, Ph.D., CPH
State Regulatory Affairs Team Leader
Syngenta Crop Protection, Inc.
P.O. Box 18300
Greensboro, North Carolina 27419-8300

Dear Dr. Abbott:

Re: Registration of the Major Change in Labeling for Cyromazine, Contained in the Pesticide Product Trigard Insecticide (EPA Reg. No. 100-654)

The New York State Department of Environmental Conservation (Department) has reviewed your application, received February 24, 2004, to register the above-mentioned product in New York State. The product contains the active ingredient cyromazine (chemical code 121301).

The application was deemed complete for purposes of review on October 4, 2004 and a registration decision is due by April 15, 2005.

Cyromazine was first registered in New York State in 1986 and has not been previously reviewed as part of the current pesticide registration program. Cyromazine is currently registered for leafminer control in leafy vegetables (except Brassica vegetables), succulent lima beans, peppers, curcurbits and tomatoes. The addition of dry beans (except cowpeas), Brassica leafy vegetables, Abyssinian cabbage, Hanover salad, turnip greens and bulb vegetables represents a major change in labeled use pattern for cyromazine in New York State. Trigard is packaged in six water soluble packets at 2.66 oz product each. The product contains 75% active ingredient, and the maximum application rate is 0.75 lb active ingredient per acre per season.

The Department of Health (DOH) stated that neither cyromazine nor the formulated Trigard Insecticide product was very acutely toxic by the oral, dermal, or inhalation routes of exposure in laboratory animal studies. The active ingredient was not irritating to the eyes, but was mildly irritating to the skin whereas the formulated product was mildly irritating to the eyes and moderately irritating to the skin (tested on rabbits). Neither cyromazine nor the formulated product was a skin sensitizer (tested on guinea pigs).

Cyromazine caused some effects in subchronic animal toxicity studies. In a 90-day rat feeding study, cyromazine caused alterations in liver weights in males at 30 milligrams per kilogram body weight per day (mg/kg/day); the no-observed-effect-level (NOEL) was 3 mg/kg/day. In a 90-day dog feeding study, cyromazine caused alterations in liver weight in males at 25 mg/kg/day; the NOEL was 7.5 mg/kg/day. Cyromazine did not cause any dermal or systemic toxicity in a 21-day dermal toxicity study in rabbits at levels up to 2,010 mg/kg/day (the highest dose tested).

Cyromazine also caused some toxicity in chronic animal feeding studies. In a chronic feeding/oncogenicity study in rats, cyromazine caused decreased body weights at 15 mg/kg/day; the NOEL was 1.5 mg/kg/day. In a chronic feeding/oncogenicity study in mice, the only effect reported was decreased body weights at a dose of 150 mg/kg/day; the NOEL was 7.5 mg/kg/day. In a six-month dog feeding study, cyromazine caused alterations in hematological parameters (hemoglobin and hematocrit) in both sexes at a dose of 75 mg/kg/day; the NOEL was 7.5 mg/kg/day. In 1986, the United States Environmental Protection Agency's (USEPA) Integrated Risk Information System (IRIS) established a reference dose (RfD) for cyromazine of 0.0075 mg/kg/day based on what was determined to be a NOEL of 0.75 mg/kg/day from the six-month feeding study in the dog and an uncertainty factor of 100 to account for interspecies extrapolation and human variability. More recently, the USEPA, Office of Pesticide Programs, recalculated an RfD for cyromazine of 0.075 mg/kg/day based on a NOEL of 7.5 mg/kg/day from the six-month feeding study in the dog and an uncertainty factor of 100 to account for interspecies extrapolation and human variability.

Cyromazine caused some developmental toxicity in offspring of laboratory animals at doses that also caused maternal toxicity. In a rat study, cyromazine caused an increase in the fetal incidence of minor skeletal variations at 600 mg/kg/day (the highest dose tested); the NOEL was 300 mg/kg/day. Maternal toxicity, characterized by clinical signs (red or clear nasal discharge) and decreased body weights, occurred at 300 mg/kg/day; the NOEL was 100 mg/kg/day. In a rabbit study, no treatment-related effects were reported for developmental toxicity at doses up to 60 mg/kg/day, the highest dose tested. Maternal toxicity consisted of reduced body weight gain and food consumption at 30 mg/kg/day; the NOEL was 10 mg/kg/day. In a multigeneration reproduction study in rats, cyromazine caused decreases in parental body weights and food efficiency at 150 mg/kg/day; the NOEL was 50 mg/kg/day. Developmental toxicity was characterized by decreased body weights at birth and through weaning at 150 mg/kg/day; the NOEL was 50 mg/kg/day. No reproductive toxicity was noted.

Cyromazine did not cause oncogenic effects in rat or mouse chronic feeding studies. This compound was also negative in a number of genotoxicity studies. The USEPA classified cyromazine as a "Group E carcinogen (evidence of non-carcinogenicity for humans)."

The USEPA established tolerances of 10 parts per million (ppm) for cyromazine residues in or on Abyssinian cabbage, seakale cabbage, turnip greens, Brassica leafy vegetable, and Hanover salad and 0.2 ppm for residues in or on garlic bulb, dry bulb onion, Rakkyo bulb, and shallot bulb. The USEPA estimated that chronic dietary exposure to these residues would be 8.3% of the chronic population adjusted dose (cPAD) of 0.075 mg/kg/day for the general U.S. population, 13% for children one to two years old, 5% for all infants less than one year old, and 7.5% for all females 13 to 49 years old. This chronic exposure analysis is based on the assumption that 100% of crops are treated and contain tolerance level residues. Actual residues and resulting exposure levels are expected to be less than this assessment estimates.

The USEPA conducted an occupational risk assessment for inhalation exposures to cyromazine during mixing, loading, and application activities via aerial sprayer or groundboom to dry beans. Risks from dermal exposures were not determined because there were no effects in two different 21-day dermal toxicity studies in rabbits at doses up to 2,010 mg/kg/day. For determining margins of exposure (MOEs) for inhalation, the USEPA compared estimated short-term exposures to a NOEL of 10 mg/kg/day from the developmental toxicity study in rabbits. Intermediate-term inhalation exposures were compared to a NOEL of 7.5 mg/kg/day from the six-month feeding study in the dog. For commercial mixer/loader/applicators, MOEs ranged between 34,000 for intermediate-term flagging sprays for aerial operations and 290,000 for short-term mixing/loading for groundboom application. These estimates assumed a maximum application rate of 0.125 pounds cyromazine per acre six times per year at seven-day intervals, as specified on the label. It was also assumed that workers wore chemical-resistant gloves, a long-sleeved shirt and pants, and chemical-resistant footwear plus socks as per label requirements. The USEPA did not estimate MOEs for post-application occupational exposure because no dermal toxicity endpoints were identified for this exposure potential and post-application inhalation exposures were expected to be negligible. Generally, the USEPA considers MOEs of 100-fold or greater to provide adequate worker protection.

The DOH briefly reviewed the environmental fate data on cyromazine. These data indicate that this chemical, like other triazine pesticides, may have the ability to leach through certain soil types and contaminate groundwater; the adsorption coefficients (Koc) in several of these soil types ranged from 81 to 1,800. These values suggest that cyromazine may have a moderate to high mobility through some soils. Some degradates of cyromazine also appear to have leaching potential. Accordingly, the Trigard label contains the Ground Water Advisory statement "A metabolite of Trigard Insecticide has been found in ground water, possibly as a result of agricultural use. Use of this product in areas where soils are permeable and water tables are shallow could result in leaching to ground water. Irrigation could increase the risk of contamination."

There are no chemical-specific federal or State drinking water/groundwater standards for cyromazine. Based on their chemical structures, cyromazine and its principal degradate, melamine, fall under the 50 microgram per liter New York State drinking water standard for "unspecified organic contaminants" (10 NYCRR Part 5, Public Water Systems). The New York State drinking water standard for the sum of "unspecified organic contaminants" and "principal organic contaminants" is 100 micrograms per liter.

The available information indicates that cyromazine was not very toxic in acute studies and was mildly irritating to the skin. Trigard Insecticide was not very acutely toxic, nor very irritating to the eyes. Trigard is a moderate skin irritant, but it is a solid formulation packaged in water-soluble bags that limit direct skin contact, and the label requires the use of appropriate personal protective equipment. Cyromazine was not oncogenic or genotoxic. While cyromazine caused some effects in subchronic and chronic toxicity studies, and caused some developmental effects at doses that also caused maternal toxicity, the expected exposure from the labeled use of Trigard Insecticide is rather low and should not pose a significant risk to the general public or to workers.

The Bureau of Habitat completed an ecological risk assessment of Trigard Insecticide and has no objection to its registration.

The Department's groundwater staff state that no environmental fate DERs were available despite attempts by the registrant to obtain them. Staff have the USEPA One-Line Summary (dated 12/23/92), the Environmental Fate & Ground Water Branch Review of a Prospective Ground Water Monitoring Study final report (dated 1/11/93), the memorandum entitled "Review of Ground-Water Issues and the Florida Prospective Ground-Water Monitoring Study for Cyromazine" (dated 5/9/95) and the Human Health Risk Assessment for Dry Beans (dated 8/30/02).

Technical Review

Unless otherwise indicated, the information presented below comes from the USEPA One-Line Summary dated December 23, 1992.

Solubility: Cyromazine has a water solubility of 1.36 x 105 mg/L.

Hydrolysis: Cyromazine is stable at pHs 5, 7, and 9.

Aqueous Photolysis: Cyromazine is stable in water at pH 7 and 25oC for one week.

Soil Photolysis: Cyromazine is stable on soil surface to a xenon arc lamp for 24 hours.

Aerobic Soil Metabolism: The half-life is 150 days, but soil type was not provided.

Anaerobic Soil Metabolism: Not provided.

Adsorption/Desorption: Collombey sand with 2.2% OM and a pH of 7.8 had a Kd of 1.35; Vetroz scllm 5.6% OM and pH of 6.7 had a Kd of 3.72; Les Evoue silm with 3.6% OM and a pH of 6.1 had a Kd of 5.29; Illaraz or. soil with a 22.9% OM and pH of 7.5 had a Kd of 26.9. (Note: these are not typographical errors-this is what is listed on the USEPA One-Line Summary.) Under the Comments section, USEPA stated that the Koc was estimated to be 200. In the 8/30/02 Human Health Risk Assessment for Dry Beans, they used a Koc of 106. They stated that leachability of cyromazine was not correlated to OM, but was influenced by pH. It did not leach as much in acidic soils.

Field Dissipation: Half-lives were listed at 84, 75-180, 204-244, 185-284, 203-146, 107 and 142 days. Kocs were listed at 1800, 208, 978, 81. No soil types were listed. Half-lives were listed as 84 days in a sandy loam, 236 days in a silt loam, 210 days in a peat soil and 83-93.3 days in a sand.

Degradate: Melamine, the major degradate, is persistent and mobile. It comprises up to 33% of the original parent material in the aerobic metabolism study. Ground Water Monitoring: Cyromazine was found in the soil at 13.2 to 24.3 ppb 157 days after last application; melamine at 23.2-33.2 ppb in the Florida ground water study.

Computer Modeling: There was not sufficient information presented to perform computer modeling.

Label Statements: Ground Water Advisory - "A metabolite of Trigard has been found in ground water, possibly as a result of agricultural use. Use of this product in areas where soils are permeable and water tables are shallow could result in leaching to ground water. Irrigation could increase the risk of contamination."

Summary: Given the lack of adequate environmental fate information submitted, the label groundwater advisory statement, comments from the USEPA regarding this active ingredient, and that this active ingredient is in the triazine family (a family of chemicals already known to leach to groundwater), staff have no choice but to recommend that this product be prohibited from use in Nassau and Suffolk Counties.

To address this concern, Trigard Insecticide will be labeled off of Long Island and will be reclassified as "Restricted Use." This Long Island prohibition and New York State "Restricted Use" status for this product will be effective January 1, 2006. The Department will also investigate adding cyrozamine, and its major degradate melamine, to the array of chemicals analyzed in its various groundwater monitoring projects.

As of January 1, 2006, Trigard Insecticide (EPA Reg. No. 100-654) will be prohibited in its sale, sale into, distribution and use in Nassau and Suffolk Counties of New York State. Also, this product will be reclassified as "Restricted Use" in New York State under rules and regulations 6 NYCRR Part 326.23(e). As such, this product will be restricted in its purchase, sale, sale into, distribution, use and possession in New York State. Furthermore, a "restricted use" product may only be purchased and used by a certified applicator in New York State, and all use and sales will be required to be reported to the Department in accordance with the Pesticide Reporting Law.

According to New York State Department of Environmental Conservation Regulations 6 NYCRR 326.3(a): "It shall be unlawful for any person to distribute, sell, offer for sale, purchase for the purpose of resale, or possess for the purpose of resale, any restricted pesticide unless said person shall have applied for, and been issued a commercial permit."

The Pesticide Reporting Law (PRL) in the Environmental Conservation Law Article 33 Title 12 requires all certified commercial pesticide applicators to report information annually to the Department regarding each pesticide application they make. Commercial pesticide retailers are required to report all sales of restricted pesticide products and sales of general use pesticide products to private applicators for use in agricultural crop production. If no sales are made within New York State, a report still must be filed with the Department indicating this is the case.

The addition of the above-mentioned New York State specific label language and the classification of the product as "restricted use" should adequately protect the groundwater resources of Nassau and Suffolk Counties.

The Department concludes that Trigard Insecticide should not have an adverse effect on the health of workers, the general public, or the fish and wildlife resources, in New York State when used as labeled.

Given the above information, the Department hereby accepts for registration the revised label for Trigard Insecticide (EPA Reg. No. 100-654) in New York State.

Syngenta Crop Protection, Inc., has agreed to amend their federally registered product label to include the New York State specific language "Not for Sale, Sale into, Distribution and or Use in Nassau and Suffolk Counties of New York" and submit the updated labeling to our Department for registration by January 1, 2006.

Enclosed is your New York State stamped "ACCEPTED" label.

Syngenta Crop Protection, Inc., is reminded that if New York State registration is requested for this product, or for any other product which contains cyromazine with an increased application rate and/or expanded use sites, the product will be considered a Major Change in Labeling and the Department will require an extensive review.

Also, if Syngenta Crop Protection, Inc., decides in the future to pursue the registration of this product in Nassau and Suffolk Counties, the EFED Environmental Fate Risk assessment, in addition to any other available environmental fate information, must be submitted.

If you have any questions, please contact Samuel Jackling, Chief of our Pesticide Product Registration Section, at (518) 402-8768.

Sincerely,

Maureen P. Serafini
Director
Bureau of Pesticides Management

Enclosures
cc: w/enc. - N. Kim/D. Luttinger - NYS Dept. of Health
R. Zimmerman/R. Mungari - NYS Dept. of Ag. & Markets
W. Smith - Cornell University, PMEP